Insulin resistance predicts endothelial dysfunction and cardiovascular risk in HIV-infected persons on long-term highly active antiretroviral therapy

Abstract

Objective-Cardiovascular disease risk among persons with HIV is likely multifactorial, thus testing a variety of available noninvasive vascular ultrasound and other surrogate tests may yield differing results. To address this issue, we assessed multiple metabolic and clinical predictors of endothelial function and carotid intima-media thickness in HIV-infected subjects and compared results with HIV-negative controls.Design-Prospective, cross-sectional study of 50 HIV-infected, healthy adults on stable highly active antiretroviral therapy matched to 50 HIV-negative controls by age, sex, race, and body mass index.Methods-Flow-mediated vasodilation of the brachial artery, carotid intima-media thickness, dual energy X-ray absorptiometry (HIV-infected subjects), and fasting insulin, lipids, and oral glucose tolerance tests were performed. Results were compared between HIV-infected and control groups.Results-Fifty percent of subjects were African-American with 34% women. Among HIVinfected, mean CD4 cell count was 547 cells/ µl; 90% had HIV RNA less than 50 copies/ml. There were no significant differences between HIV-infected and control subjects with regard to brachial artery flow-mediated vasodilation or carotid intima-media thickness. In multivariate analyses of the HIV cohort, independent predictors of endothelial dysfunction (lower flow-mediated vasodilation) were increasing insulin resistance, greater alcohol consumption, and higher baseline brachial artery diameter (P < 0.05); predictors of increased carotid intima-media thickness were hypertension, higher trunk/limb fat ratio, and insulin resistance (P < 0.05).Conclusion-In this HIV cohort on modern highly active antiretroviral therapy with well controlled HIV, there were no significant differences with regard to preclinical markers of cardiovascular disease. Insulin resistance was a strong predictor of impaired brachial artery flowmediated vasodilation and increased carotid intima-media thickness, and may be an important cardiovascular disease risk factor in the HIV population.

Review of Cardiovascular Disease in HIV-Infected Women

“…Carotid Intimal Medial Thickness can be a useful marker of atherosclerosis and has been shown to correlate with CV risk factors and predict stroke and myocardial infarction in the general population [17]. Results of CIMT in HIV-infected women have been mixed with a few studies finding no significant difference between HIV-infected females and HIVuninfected females [15,18]. Increased CIMT has been associated with several CV risk factors, however.…”

“…The Framingham risk score has been the most common risk assessment tool used to evaluate the risk of developing CHD in HIV-infected men and women. Studies demonstrate that HIV-infected women have low Framingham risk scores [10,14,15], but there are no studies validating the FRS in this population. The Data Collection on Adverse Events of Anti-HIV Drugs (DAD) equation was derived to assess the potential increased risk of CHD in HIV-infected people using combination ART.…”

Influence of Antiretroviral Therapy on the Metabolic Profile of People Living with HIV Followed at University Hospital, Cotonou, Benin

“…The impact of ART on the occurrence of metabolic syndrome is due to the mechanism of action of ARVs Drugs which determine dysfunction of lipid and glucose metabolism of patients [12]- [15]. The high prevalence of metabolic syndrome in patients exposes them more to cardiovascular disease [16] [17] and diabetes [18] [19]. The risk to develop diabetes in our patients treated was 6 times that of untreated.…”

High-Fat Meals Do Not Impair Postprandial Endothelial Function in HIV-Infected and Uninfected Men

“…Previously both traditional and novel risk factors have been implicated in endothelial dysfunction and cardiovascular disease risk in HIV-infected individuals. For example, increasing insulin resistance predicted endothelial dysfunction in an HIV-infected cohort whose mean FMD was similar to that of matched HIV-uninfected controls, 15 and current injection drug use and hazardous drinking have also been shown to be associated with impaired FMD. 13 Current evidence suggests that endothelial dysfunction caused by circulating inflammatory mediators precedes and contributes to hypertension 37,38 ; therefore, rather than causing impaired FMD, elevated diastolic blood pressure may, in fact, reflect a downstream effect of antecedent peripheral vascular dysfunction.…”

“…[6][7][8][9] HIV has also been associated with impaired FMD in several studies, [10][11][12][13] though this is not a universal finding. 14,15 Impaired endothelial function precedes atherosclerosis and is independent of other cardiovascular (CV) risk factors. [16][17][18][19] Premature CV disease is of concern in HIV-infected persons, especially those on antiretroviral therapy (ART).…”